BAG3 Promoted Starvation-Induced Apoptosis of Thyroid Cancer Cells via Attenuation of Autophagy

BAG3 Promoted Starvation-Induced Apoptosis of Thyroid Cancer Cells via Attenuation of Autophagy
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BAG3 通过减弱自噬促进饥饿诱导的甲状腺癌细胞凋亡

DOI:
10.1210/jc.2014-1779
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发表时间:
2014-11-01
影响因子:
5.8
通讯作者:
Du, Zhen-Xian
Du, Zhen-Xian
中科院分区:
医学2区
文献类型:
--
作者:
Li, Si;Zhang, Hai-Yan;Du, Zhen-Xian

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背景:BAG 3在许多细胞过程中起着调节作用。近年来,它在选择性自噬激活中的作用引起了人们的广泛关注。此外,我们最近报道,BAG 3是牵连在一个BECN 1独立的自噬,即noncanonical autophagy.Objective:目前的研究旨在探讨BAG 3在典型的自噬触发Earle的平衡盐溶液(EBSS)starving.Setting和设计:EBSS的完全培养基的替代被用来触发典型的自噬。使用实时RT-PCR和Western blot测量BAG 3表达。通过Western印迹使用LC 3-II转换和p62/SQSTM 1积累以及通过免疫荧光染色使用LC 3的点状分布来监测自噬。结果:EBSS饥饿可明显抑制BAG 3的表达,但对BAG 3的表达无明显影响。BAG 3的强制表达抑制了自噬,并促进了饥饿引起的甲状腺癌细胞的凋亡。此外,在自噬抑制剂的存在下,BAG 3对凋亡细胞death.Conclusions的增强作用减弱:这些结果表明,BAG 3促进饥饿的甲状腺癌细胞的凋亡细胞死亡,至少部分通过自噬衰减。2014年度)
Context: BAG3 plays a regulatory role in a number of cellular processes. Recent studies have attracted much attention on its role in activation of selective autophagy. In addition, we have very recently reported that BAG3 is implicated in a BECN1-independent autophagy, namely noncanonical autophagy.Objective: The current study aimed to investigate the potential involvement of BAG3 in canonical autophagy triggered by Earle's Balanced Salt Solution (EBSS) starvation.Setting and Design: Replacement of complete medium with EBSS was used to trigger canonical autophagy. BAG3 expression was measured using real-time RT-PCR and Western blot. Autophagy was monitored using LC3-II transition and p62/SQSTM1 accumulation by Western blot, as well as punctate distribution of LC3 by immunofluorescence staining. Cell growth and apoptotic cell death was investigated using real-time cell analyzer and flowcytometry, respectively.Results: BAG3 expression was potently reduced by EBSS starvation. Forced expression of BAG3 suppressed autophagy and promoted apoptotic cell death of thyroid cancer cells elicited by starvation. In addition, in the presence of autophagy inhibitor, the enhancing effect of BAG3 on apoptotic cell death was attenuated.Conclusions: These results suggest that BAG3 promotes apoptotic cell death in starved thyroid cancer cells, at least in part by autophagy attenuation. 2014)